Portrait Prof. Zweckstetter

Prof. Dr. Markus Zweckstetter

Group leader

German Center for Neurodegenerative Diseases
Ber. C-1, Raum 1.212
Von-Siebold-Str. 3a
37075 Göttingen

+49 (0) 551 / 61181

Group members

Name Telefon
Petra Breiner, Office assistant +49 (0) 551 / 201-2200
Dr. Nasrollah Rezaei-Ghaleh, Postdoc +49 (0) 551 / 61184
Dr. Javier Oroz, Postdoc +49 (0) 551 / 61186
Dr. Garima Jaipuria, Postdoc +49 (0) 551 / 61185
Dr. Filippo Favretto, Postdoc +49 (0) 551 / 61188
Dr. Aldo Roman Camacho Zarco, Postdoc +49 (0) 551 / 61188
Dr. Harindranath Kadavath, Postdoc +49 (0) 551 / 61187
Dr. Tae-Kyung Yu, Postdoc +49 (0) 551 / 61186
Dr. Susmitha Ambadipudi, Postdoc +49 (0) 551 / 61188
Dr. Lukasz Jaremko, Postdoc +49 (0) 551 / 201-2217

Selected publications

Structure of the mitochondrial translocator protein in complex with a diagnostic ligand.

Jaremko L, Jaremko M, Giller K, Becker S, Zweckstetter M.>/p> Science. 2014 Mar 21;343(6177):1363-6. doi: 10.1126/science.1248725

Hsp90-tau complex reveals molecular basis for specificity in chaperone action.

Karagöz GE, Duarte AM, Akoury E, Ippel H, Biernat J, Morán Luengo T, Radli M, Didenko T, Nordhues BA, Veprintsev DB, Dickey CA, Mandelkow E, Zweckstetter M, Boelens R, Madl T, Rüdiger SG. Cell. 2014 Feb 27;156(5):963-74

ß-synuclein aggregates and induces neurodegeneration in dopaminergic neurons.

Taschenberger G, Toloe J, Tereshchenko J, Akerboom J, Wales P, Benz R, Becker S, Outeiro T, Looger L, Bähr M, Zweckstetter M, Kügler S. Ann Neurol. 2013 Mar 28. doi: 10.1002/ana.23905. [Epub ahead of print]

Cold denaturation of a protein dimer monitored at atomic resolution.

Jaremko, M., Jaremko, Ł., Kim, H.-Y., Cho, M.-K., Schwieters, C. D., Giller, K., Becker, S., Zweckstetter, M. Nat. Chem. Biol. 2013, DOI 10.1038/NChemBio .1181.

Mechanistic Basis of Phenothiazine-Driven Inhibition of Tau Aggregation.

Akoury, E., Pickhardt, M., Gajda, M., Biernat, J., Mandelkow, E., Zweckstetter, M.  Angew. Chem. Int. Ed. 2013, DOI 10.1002/anie.20120829.

Functional dynamics in the voltage-dependent anion channel.

Villinger, S., Briones, R., Giller, K., Zachariae, U., Lange, A., de Groot, B. L., Griesinger, C., Becker, S., Zweckstetter, M. Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 22546-22551.

Structural polymorphism of 441-residue tau at single residue resolution.

Mukrasch, M. D., Bibow, S., Korukottu, J., Jeganathan, S., Biernat, J., Griesinger, C., Mandelkow, E., Zweckstetter, M. PLoS Biol. 2009, 7, e34.

Pre-fibrillar alpha-synuclein variants with impaired beta-structure increase neurotoxicity in Parkinson's disease models.

Karpinar, D.P., Balija, M.B., Kügler, S., Opazo, F., Rezaei-Ghaleh, N., Wender, N., Kim, H.Y., Taschenberger, G., Falkenburger, B.H., Heise, H., Kumar, A., Riedel, D., Fichtner, L., Voigt, A., Braus, G.H., Giller, K., Becker, S., Herzig, A., Baldus, M., Jäckle, H., Eimer, S., Schulz, J.B., Griesinger, C., Zweckstetter, M. EMBO J. 2009, 28, 3256-3268.

Structure of the human voltage-dependent anion channel.

Bayrhuber, M., Meins, T., Habeck, M., Becker, S., Giller, K., Villinger, S., Vonrhein, C., Griesinger, C., Zweckstetter, M., Zeth, K. Proc. Natl. Acad. Sci. U.S.A. 2008, 105, 15370-15375.

Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein.

Bertoncini, C. W., Jung, Y. S., Fernandez, C. O., Hoyer, W., Griesinger, C., Jovin, T. M., Zweckstetter, M. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 1430-1435.

Die vollständige Publikationsliste finden sie hier.

Curriculum Vitae

Markus Zweckstetter studied physics at the Ludwig Maximilians University in Munich. He wrote his Ph.D thesis under the supervision of Tad Holak at the Max Planck Institute for Biochemistry in Martinsried and received his Ph.D from the Technical University of Munich. Subsequently, he worked from 1999 to 2001 as a postdoctoral fellow in Dr. Adrian Bax’s group at the National Institutes of Health in Bethesda, Maryland, USA. He has headed the research group “Structure determination of proteins using NMR” at the Max-Planck-Institute for Biophysical Chemistry since 2001. Since June 2012 he is heading the senior research group “Structural Biology in Dementia” at the German Center for Neurodegenerative Diseases (DZNE) Göttingen. Since December 2012 he is also professor at the University Medical School, Göttingen.

Areas of investigation/research focus

The research performed in the research group “Structural Biology in Dementia” tackles the structural biology challenges faced today in dementia and neurodegeneration that is intrinsically disordered proteins, protein aggregates, big proteins, nucleosome complexes, proteins in membranes. The work builds on our expertise in structural biology, especially via the use of Nuclear Magnetic Resonance (NMR) and biophysics. In addition, we are interested in the structure-based design and optimization of small molecules that shall interact with specific target proteins as biomarkers, for imaging purposes or treatment of neurodegenerative diseases.

Examples of our work include:

  • We elucidate the structural and dynamic properties of the Tau protein and its different isoforms in different conformational states at atomic resolution (collaboration with E. und E.M. Mandelkow, DZNE-Bonn). In addition, we study the mechanism of action of aggregation inhibitors as well as the nature of the induced species of the Tau protein, the amyloid-beta peptide, the prion protein and the Parkinson-related protein a-synuclein.
  • We study the dynamic structure of membrane proteins important for neurodegeneration. Our aim is to characterize structural ensembles of higher complexity and provide access to a wide range of functional dynamics. The chosen membrane proteins are linked to several human pathologies that cannot be treated because structural information at atomic resolution is missing. Our studies should lay the basis for the development of novel, selective and improved therapies for age-related neurodegeneration.
  • We investigate the structure of the nucleosome, its organization into higher-order structures and its interaction with chromatin readers that recognize specific histone-modifications. We foresee that such approaches will allow us to eventually target disease associated chromatin signatures via the development of small molecule drugs that specifically modulate such interactions.